Summary

Etelcalcetide (Parsabiv) is a synthetic peptide composed of D-amino acids that acts as an allosteric activator of the calcium-sensing receptor (CaSR). It is approved for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on haemodialysis. Administered intravenously at the end of each dialysis session, etelcalcetide lowers parathyroid hormone (PTH), calcium, and phosphate levels. It represents a significant peptide therapeutic with robust Phase 3 evidence. Research use only — not for self-administration.

Mechanism

Etelcalcetide is an allosteric activator of the calcium-sensing receptor (CaSR). It is an 8-amino-acid peptide composed of D-amino acids with a C-terminal cysteine that forms a disulphide bond with serum albumin at cysteine-34, creating a long-acting depot. The peptide's N-terminal D-amino acid sequence binds allosterically to the CaSR on parathyroid chief cells, sensitising the receptor to ambient calcium levels and thereby suppressing PTH secretion. The D-amino acid composition confers resistance to proteolytic degradation, extending the functional half-life.

Evidence base

Phase 3 (two pivotal trials): 1,023 CKD patients on haemodialysis with SHPT. Primary endpoint (≥30% PTH reduction): 78.5% vs 10.1% placebo (Trial A) and 76.5% vs 9.6% placebo (Trial B), both p<0.001 (Block et al., JAMA, 2017).

Active comparator trial: Etelcalcetide vs cinacalcet in 683 patients. Superiority for ≥30% PTH reduction: 68.2% vs 57.7%, p=0.004 (Block et al., JAMA, 2017).

Safety: Hypocalcaemia is the primary safety concern. FDA warning for QT prolongation and seizure risk (2021).

Evidence grade: Strong — Multiple Phase 3 RCTs, active comparator study, regulatory approval.

Protocols

Approved clinical protocol:

  • Starting dose: 5 mg IV bolus, 3×/week at end of haemodialysis
  • Adjustment: +2.5 or 5 mg increments every 4 weeks, max 15 mg 3×/week
  • Monitoring: PTH every 2–4 weeks during titration; corrected calcium ≥2.1 mmol/L required

⚠️ Research use only. Not for self-administration.

UK Status: POM (prescription-only medicine)

Etelcalcetide (Parsabiv) is licensed by the EMA (2017) and available on the NHS for secondary hyperparathyroidism in CKD patients on haemodialysis. Requires specialist renal prescription. Not a controlled substance. Research-grade material legal for laboratory research.

Vendor notes

As a licensed POM, etelcalcetide is not available from research peptide vendors. Clinical supply is through licensed pharmaceutical distribution. Researchers should consult accredited chemical suppliers for laboratory-grade material.

References

  1. Block GA, Bushinsky DA, Cheng S, et al. Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials. JAMA. 2017;317(2):146–155. doi:10.1001/jama.2016.19456
  2. Block GA, Bushinsky DA, Cunningham J, et al. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA. 2017;317(2):156–164. doi:10.1001/jama.2016.19457
  3. FDA. Parsabiv (etelcalcetide) prescribing information. Amgen, 2017. Updated 2021.
  4. EMA. Parsabiv European Public Assessment Report (EPAR). EMA/CHMP, 2017.
  5. Subramanian R, Zhu X, Kerr SJ, et al. Nonclinical pharmacokinetics, pharmacodynamics, and toxicology of etelcalcetide (AMG 416), a novel calcimimetic peptide. Am J Nephrol. 2016;43(4):251-261.